Bile acid accumulation induced by miR-122 deficiency in liver parenchyma promotes cancer cell growth in hepatocellular carcinoma.

ABSTRACT: Liver is the central player in maintaining metabolic homeostasis of bile acids (BAs), but how BA is tightly controlled is still largely unknown, and the role of BAs in the development of hepatocellular carcinoma (HCC) remains controversial. Here, we discovered that elevated hepatic BAs were associated with miR-122 downregulation during liver regeneration, steatosis, and fibrosis. In vivo mouse models showed that miR-122 deficiency of liver parenchymal cells (hepatocytes) in paracancerous tissues resulted in significantly increased BA levels and altered hepatic BA spectrum, thus promoting liver tumor burden, which could be abated by administration of BA sequestrant. Mechanistically, miR-122 attenuated BA production by directly targeting BA synthesis gene HSD3B7, thereby inhibi

SUBMITTER: Huang JH 

PROVIDER: S-EPMC12166698 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature